Elevated levels of certain plasma lipoproteins are accompanied by increased risk of atherosclerotic cardiovascular disease. Most patients with hyperlipoproteinemia fall into the high risk categories. Understanding of the structure of lipoproteins has increased in the last few years, and several apolipoproteins have been purified. The apoproteins play important roles not only in the structure but also in the metabolism of lipoproteins. Therefore, aberrations in the structure and/or metabolism of apoproteins could be important in the pathogenesis of hyperlipoproteinemia. Yet it has not been possible to quantify most of the apoproteins either in whole plasma or in lipoproteins because specific and sensitive assays for most were not available until very recently. The objective of this project is to develop radioimmunoassays for the apoprotein of the required sensitivity and specificity to measure their concentrations in whole plasma and its lipoprotein fractions, in normal subjects and in patients with dyslipoproteinemia. Studies will be carried out in "basal" state, on therapy, and following other metabolic and dietary perturbations. Data on apoprotein levels in plasma and in various density fractions will be collected in unbiased populations and in families. In addition, assays specific for the various structural regions of apoproteins will be developed and applied to studies of the structure and metabolism of lipoproteins. The proposed studies should result in a better understanding of the pathophysiology, modes of inheritance and modes of action of the therapies for the hyperlipoproteinemias. It is hoped that increased understanding will lead to effective means of control of lipoprotein metabolism and the prevention of atherosclerotic complications. BIBLIOGRAPHIC REFERENCES: Schonfield, G., Bradshaw, R.A. and Chen, J-S.: Structure of High Density Lipoprotein: the Immunologic Reactivities of the Carboxyl and Amino Terminal Regions of Apolipoprotein A-I, J. Biol. Chem. 251: 3921-3926, (in press), l976. Chen, J-S., Schonfield, G., Roy, R.: Interactions of Phospholipids with ApoA-I. Submitted to American Heart Association, (in press), l976.